Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.
Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.
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吲哚尿毒症溶质通过磷脂酰丝氨酸暴露和微粒释放增强红细胞的促凝血活性
DOI：
10.3390/toxins7114390
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发表时间：
2015-10-28
期刊：
影响因子：
4.2
通讯作者：
Shi J
中科院分区：
文献类型：
--
作者：
Gao C;Ji S;Dong W;Qi Y;Song W;Cui D;Shi J
尿毒症患者血液中吲哚类尿毒症溶质的蓄积增加会导致血栓事件的风险上升。红细胞（RBCs）是循环中数量最多的血细胞，可能是这些溶质的一个特殊作用靶点。然而，尿毒症溶质硫酸吲哚酚（IS）和吲哚 - 3 - 乙酸（IAA）对红细胞促凝血活性（PCA）的影响尚不清楚。在此，我们用IS和IAA（尿毒症患者体内所报道的平均浓度和最大浓度）处理来自健康成年人的红细胞。用Alexa Fluor 488 - 乳黏素标记红细胞的磷脂酰丝氨酸（PS）暴露及其微粒（MPs）释放情况，并通过流式细胞仪进行检测。用Fluo 3/AM标记的胞质Ca²⁺（[Ca²⁺]）通过流式细胞仪进行分析。通过凝血时间和纯化凝血复合物测定来评估PCA。我们发现，在IS和IAA的平均浓度下，红细胞的PS暴露、MPs产生以及随之而来的PCA增强，并在尿毒症最大浓度时达到峰值。此外，128 nM的乳黏素（一种PS抑制剂）抑制了红细胞和红细胞微粒（RMPs）90%以上的PCA。吲哚类尿毒症溶质导致的红细胞凋亡或损伤至少部分是由于胞质[Ca²⁺]的增加。我们的研究结果表明，尿毒症溶质IS和IAA中的红细胞凋亡通过释放RMPs和暴露PS在血栓形成中起重要作用。乳黏素在这一过程中是一种有效的抗凝剂。
Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca2+ ([Ca2+]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca2+]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process.
影响因子：
4.2
作者：
Frauenfeld L;Alzoubi K;Abed M;Lang F
通讯作者：
Lang F